Hi, All. There have been a few recent comments by others suggesting that, following their discontinuance of an RLS medication, their RLS symptoms lessened or, in some instances, disappeared. Some comments concerned "patches," and some concerned tablets or capsules. Not all concerned dopamine agonists. As my experience is with the latter, that is the subject.
I took pramipexole daily for 20+ years, beginning some time around 1998 and continuing to 2022. Though I do not recall when I first experienced augmentation, I recall that it was around the same time that generic variations of Mirapex became available. In time, the initial dose of pramipexole became less effective, and my RLS discomfort worsened.
I could not sit comfortably on my sofa (loveseat) to watch TV @ 6:00 PM. Sitting at my computer after @ 8:00 PM became unbearable. This discomfort would reach its peak sometime in the early morning hours and then subside, after which I would fall asleep. But there were some days and evenings during which I did not suffer. I checked the day's weather out of habit (years of riding a motorcycle) but also in desperate hope of a coming thunderstorm to wash out the humidity. A thunderstorm foreshadowed a day or two of relief from RLS. And so it went. ...Until last year.
As I've posted elsewhere, for much of last year, I went through DAWS. After successfully titrating off pramipexole (and daily doses of Tramadol; and Vicodin as needed), I briefly was drug free. Though I continued to suffer horrific discomfort in the late evening and early morning hours, I noted that my late mornings, afternoons, and early evenings were different. Minor RLS discomfort aside, if I chose to do so, I now could sit comfortably on my sofa and watch TV day long, and likewise could sit at my computer. Minor RLS discomfort aside, I had become RLS-free from ~8:00 AM - ~9:00 PM.
To be sure, there is no free lunch. My RLS discomfort begins to rise ~10:00 PM and reaches its zenith ~1:00 AM - ~3:00 AM. This zenith is higher than the altitude reached during the 20+ years that I was on pramipexole, and daily competes with the worst RLS discomfort ever before experienced by me. It is exceeded by duration and intensity only by the DAWS Hell.
I now am taking pregabalin (1 x 75 mg ~10:00 PM; 1 x 75 mpg ~Midnight; and as/if needed, 1 x 75 mg ~2:00 AM). Preliminary observations are favorable. Unfortunately, though the pregabalin offers relief, the duration of its relief is unpredictable and brief. I do not know if the 3rd dose will be necessary until RLS discomfort has broken thru.
Some literature has suggested that following dopamine agonist-induced augmentation, the sufferer's brain is "rewired." It further has been suggested that, once a brain has been re-wired, some RLS medicines--including pregabalin--may not work. However, I have not yet found any literature that suggests that this rewiring may eventuate in other collateral consequences, both good and bad. In my case, the good has been a lessening of discomfort in the late morning, afternoon, and early evening hours; the bad has been an increased intensity and regularity of the discomfort in the early morning.
It’s probably time we explored ways to up-regulate our DA down-regulated D2/3 dopamine receptors and we also need to down-regulate our excitatory D1 receptors that were up-regulated due to the DAs as well.
Anaerobic exercise and severe calorie restriction have been shown to up-regulate D2 receptors in non-RLS subjects. I think what we really need to do is find benign or even healthy dopamine ANTAGONISTs which should do just the opposite of the dopamine AGONISTs. They have to be short-acting and taken in the morning. It all depends on how desperate one is. Benedryl, Zantac and Melatonin are all dopamine antagonists.
I think Berberine might be a better option than the aforementioned. Right now the Michael J Fox foundation is looking into Berberine for Parkinson’s. It’s also supposed to be beneficial for Alzheimer’s and MS, as well as Type 2 diabetes, and high cholesterol. frontiersin.org/articles/10...
RKM7 took berberine for 3 months after Gabapentin and ferrous bisglycinate gave her decent relief but not 100%. She’s not sure whether it was the berberine or just time, but she’s basically at 100% now. She had been on DAs for around 15 years. People who are withdrawing from the DAs should search her username and read her story.
Berberine is the only substance I could find that not only up-regulates (by antagonizing) our D2s, but also down-regulates the excitatory D1s, by agonizing them. The DAs (especially Mirapex) antagonize/block the D1s which makes them grow big and strong. It is speculated that it is actually these up-regulated D1s that cause DAWS.
Within that article it states that: “Berberine can also inhibit the release of NE via activation of adrenergic α2 autoreceptors21 and can affect DA in a manner that antagonizes D2 and agonizes D1 receptors.” And that my friend is exactly what people post-DA need to do. Btw, in the above quote DA means dopamine, NOT dopamine agonist.
in reply to
Good evening, SalemLake, and thank you for your informed reply.
I try to be responsive to the replies to my comments, but I am at a loss now, as any attempt by me to intelligently respond to your reply would require a technical expertise that I lack.
To the extent that I was able to understand the major point--which I infer to mean that an altogether different approach is needed to address this affliction--I concur. Presciently, my user name said as much.
With due respect to various of the organizations that purport to provide support to persons afflicted with RLS, some seem to have lost sight of their original objectives and instead have devolved into just another venue for collecting membership dues, soliciting contributions, funding any research project no matter inane and pointless so long as it has "RLS" in its proposal, and pimping for the orthodoxy de jure of so-called "sleep experts." Twenty years on, the same bums who championed Mirapex as a successor to Sinemet on the ground that the former would not lead to augmentation now disclaim any responsibility for doing so.
I do not know where the solution to this syndrome may lay. I am not sure if I will live to see it. As likely as not it may be found by happenstance as some persons afflicted with multiple disabilities may inadvertently discover relief from RLS while taking a medication prescribed for an altogether different purpose.
Be well.
in reply to
This article gives me hope. It shows that genetically obese rats have smaller and fewer D2 receptors, kind of like us with RLS. Calorie restriction increases those receptors bnl.gov/newsroom/news.php?a...
We need to figure out a way to do this …to us.
This article too: pubmed.ncbi.nlm.nih.gov/128... There are numerous people on here who find that if they do a nightly fast - say from 7pm to 9am - their RLS is a lot better.
We can sit on our hands and pray that the scientific community finds something that will help us or we can figure it out ourselves.
Here’s a line from that article: “An additional interesting feature of berberine is that it may have efficacy as an antidepressant. Berberine may act as a natural monoamine oxidase inhibitor (MAOI) thereby helping to potentiate or prolong the effects of norepinephrine and serotonin. Mice treated with berberine intraperitoneally (5mg/kg) for 15 days showed a 29% increase in norepinephrine a 19% increase in serotonin (19%) and a striking 52% increase in dopamine.”
I should explain that increased dopamine, as indicated above, does not translate to relief from RLS symptoms. If anything, berberine seems like it will make symptoms worse so you want to take it in the morning. The berberine BLOCKS the D2/3 dopamine receptors which translates to more dopamine because it’s uptake is being inhibited. Blocking dopamine receptors will make them increase in size and number. That’s what we want. The above is only true with berberine that has been altered to be able to cross the blood brain barrier.
Berberine, unaltered, will stay in the gut, kind of like bran, and make its way to the large intestine, rather than the bloodstream. But that’s ok too because within the gut it stimulates certain micro-organisms to produce l-dopa. This micro-organism-produced dopamine then enters the blood and is able to cross the BBB. The Michael J Fox Foundation is betting the farm on this one. That’s exactly what Parkinson patients need - more dopamine. They don’t necessarily want increased D2 receptors because theirs are already up-regulated beyond normal due to the disease. Fascinating read!!!! parkinsonsnewstoday.com/new...
in reply to
Hi, SalemLake, and that you for your further reply.
Coincidentally, I recently decided to lose a few pounds. I wonder what impact, if any, this may have had on my positive finding that my daytime, afternoon, and early evening RLS discomfort now are more bearable? If it turns out that the supply of dopamine is "limited" and that its ability to control RLS is proportional to the weight of the person upon whom that quantity acts, it would be logical to infer that a loss of weight might relieve RLS while the gaining of weight might exacerbate RLS.
With apologies if I've misinterpreted, the articles on the effect of diet on dopamine are somewhat dated. It may be that the findings of those studies were determined not worth further pursuit? Time will tell whether or not Berberene or some derivative thereof may relieve RLS. But since it is available OTC, I wonder why it is not at the forefront of those plants that routinely are touted as relieving RLS (e.g., Chamomile, St. John's Wort; Valerian Root)?
Hi Sue. No, I know exactly what I’m talking about. Drugs that lessen the symptoms of RLS like DAs, possibly tramadol, and Sinemet will make our already pathetic dopamine receptors even more pathetic over time. Substances that “antagonize” dopamine and block our D2/3 receptors and make the symptoms of RLS worse, like the aforementioned drugs, should up-regulate our receptors, theoretically.
It’s time to take back our receptors from these wrongfully prescribed drugs like Prami. I believe the way to do that is with short-acting dopamine antagonists like berberine.
In addition to being histamine blockers they also block dopamine receptors. See below paragraph:
Motion SicknessLaura Barritt, in xPharm: The Comprehensive Pharmacology Reference, 2007Standard TherapiesAnticholinergics and antihistamines are used prophylactically to prevent motion sickness. While these drugs principally target histamineand muscarinic receptors, in the brain, some may block dopamine receptors as well. All three of these receptor systems are involved in emesis following vestibular imbalance Taylor (2002).
What do you think about the idea of people trying to up-regulate their receptors who are coming off the DAs? If the DAs can down-regulate our receptors do you think it’s possible we can do just the opposite with certain substances?
Hi RLSIconoclast,Thank you for sharing your hellish journey with pramipexole, and beyond. I can only say that you have done amazingly well to wean yourself off such difficult medications. I can appreciate the problems you have encountered. You have documented everything so well too. And have found relief for some of your day at least. The different levels of RLS experienced by yourself are also similar to mine. If I get over tired/ stressed my RLS goes off the scale and it takes hours to reduce it to a more bearable level. I have not yet reduced my pramipexole. It still offers some relief with a regular dose of opioids throughout the day, (35mg). These were prescribed for another two conditions , so I have been lucky that my GP has recognised that they do work. For now, while I grapple with severe arthritis, bipolar disorder, and Crohn's disease I will remain on them. I'm taking ferritin and gentle iron, magnesium and zinc, vitamin c.
The rewiring you mention is something I have just recently heard a little about. It is another problem to adjust to.
Salem Lake has a wealth of knowledge and can offer advice much more than I'm able to.as well as Sue Johnson and Jools. Thank goodness for this site in supporting us through this ghastly disease, so misunderstood by the medical profession in general.
Good morning, pennygates, and thank you for your reply. I am reluctant to mention by name some of the many who have offered their many insights and others whose comments and replies I have read since happening on this site lest I offend many others whose names I might inadvertently omit. But certainly SalemLake, Jools, ChrisColumbus are among them. And of course SueJohnson (Though I am not sure why masturbation rather than heterosexual sex it touted as providing temporary respite from RLS.)
By experience, the hardest part of titrating off pramipexole is the last bit. In my case, my ever-dwindling supply of Tramadol and Vicodin both failed me when I needed them most. And, as I've often posted elsewhere, though my now former "sleep expert" neurologist kept pushing metahdone on me, my unwillingness to sign a PMP and perceived stigma of being a junky meant that the latter medication was not an option. Hopefully, the opiates will work for you if/when you rid yourself of dopamine agonist poison.
It is unfortunate that you suffer from other maladies. So many of us do as well. Though I make no comparison with you, I do mention that, in the coming weeks, I am to visit with a pulmonologist and a cardiologist to hopefully diagnose why I suddenly have breathing problems/chest tightness. Having thus far been thoroughly examined by my GP, undergone blood tests, an EKG, and a thoracic ultrasound, and visited with my neurologist, the answer continues to elude.
Somewhat ironic that, after about four centuries, perhaps the best medication for RLS is what Dr. Willis first prescribed: opiates. When taken for pain, they appear less likely to lead to addiction, have the fewest side effects, and offer the greatest relief. In the case of Vicodin, it never relieved my RLS discomfort; rather, I just didn't mind RLS so much. Tramadol worked like a champ. Unfortunately, the relief accorded by pregabalin is as unpredictable as is RLS: having exhausted my authorized dose (not to exceed 3 x 75 mg within 24 hours), I am now wide-awake at 2:30 AM local time (Virginia) unable to sleep due to nagging RLS which is yet to reach its apogee as it haunts the night sky above my bed.
Hi, SueJohnson. I Infer that you are a good sport, and wouldn't mind satire. In anticipation of same, I composed a vignette--a Twilight Zone episode. If offensive, please let me know and I will delete. I've made the tale with a British flavour--another commenter elsewhere expressed concern that I might be Americanizing a British website. Names are fictional; any resemblance to persons or places is coincidental.
Prologue
The scene: Rod Serling is standing in the foreground, cigarette in hand. Behind him is a row of homes in a gentrified London neighborhood. In the driveway of one home is a Range Rover; in the driveway of another, a Jaguar. With one exception, the hedges are manicured; with the same exception, each house is occupied by a married couple. The exception: Mr. Oliver Worthington. The date is August 31, 1988.
Rod Serling: "Submitted for your approval is this gentrified London neighborhood. There are many residents, but tonight we focus on three. In one home, we find a recently and happily married couple: Derek and Abigail St. James. Before jointing the SAS, Derek came to public light as one of the highest ranked Outside Centres in the history of Rugby. Abigail, the former Ms. British Isles, was Derek's high school sweetheart. In the other home, we find Oliver Worthington, the owner of a barbershop who, when not giving haircuts, fancies himself a latter-day Sir Issac Newton.
"Abigail and Derek are unapologetic heterosexuals. They are in perfect health. Whenever and wherever the opportunity presents, they enjoy each other's company to the fullest. Mr. Worthington, however, is a chronic masturbator. He does so to relieve an odd disorder that he has compared to worms crawling inside his legs. It is called RLS.
"The three are close friends, often visiting each other's home. Our story might end here. But on this night, as we are about to find, things do not go as planned. For Mr. Worthington finally has succeeded where others before had failed. Mr. Worthington has invented a time travel machine. And this, is The Twilight Zone.
Act One - Scene One
Downtown London, late afternoon. Mr. Worthington has completed his last haircut of the day. He is anxious to return home to try out his time machine. He debates whether he has time for one last masturbation before going home, or if instead he should dedicate the few minutes' time to cleaning his razor. He decides in favor of neither. He scurries out, barely remembering to lock the front door. Noticing his razor still in hand, he places same in his rear pocket without washing the dried blood.
Abigail and Derek St. James are at home. Having returned from a mission in The Middle East, they are anxious to consummate the return with heterosexual pleasure. Treating the booth that housed Mr. Oliver Worthington's latest device as nothing more than a convenient location for their evening tryst, they tried the front door to Mr. Worthington's house, delighted to find that it had been left unlocked. When they entered within the booth, they were only partly surprised to find that it had been adorned with nude photographs of Abigail as she lay in the back of her house sunbathing. The booth was, after all, within the home of a chronic masturbator.
Within the booth was a contraption; and within the contraption was a dial. The dial appeared to be a gauge. But it was not a clock. Nor was it a meter to measure voltage or current. Its gradations were listed only in magnitudes of one hundred. The meaning eluded the couple. For now, the meter registered at the 100 mark. And there was a curtain at the entrance to the booth, and a lever similar to what one might pull to close the curtain. The couple pulled the lever.
Act One - Scene Two
A dark, dank street somewhere near London. A perfect venue to complete their intended heterosexual pleasure. For now, they would ignore the unfamiliar venue. Each quickly disrobed. Instinct did the rest. Out of nowhere, a Constable walked bye. Fully unclothed, the couple otherwise looked no different than any other persons he earlier had encountered on his evening rounds. " 'ello, 'ello, you two," he chimed. "Don't you know there's a Ripper going around 'ere." "Get on with yourselves before I run you in. Or worse still, before the Ripper has 'is way with you."
Abigail and Derek stared at each other in disbelief. "The Ripper"? A tattered Broadsheet drifted bye, caught and read by Derek in the evening's dim light. It is August 31, 1888--one hundred years earlier than when they last had entered Mr. Oliver Worthington's house. The heterosexuals considered themselves lucky. Jack the Ripper had not killed couples. Nor had the Constable arrested them despite having been found in flagrante delicto. They were, after all, engaged in heterosexual sex.
Act One - Scene Three
Mr. Worthington prepared for an evening of masturbatory delight. His expectations were foiled when he noticed something amiss. The time travel machine appeared to have been used. With the perfume of Abigail still wafting, the worst was suspected. He now must follow the path of his friends to retrieve them from wherever they may have gone.
Without stopping to change clothes or to masturbate, in an instant, he pulls the lever rather than his member. He is back-in-time to August 31, 1888. The significance of the date eludes him. It is dark. And his needs have not yet been fulfilled. As his predecessors had before him, he quickly disrobes. But unlike his predecessors, he pleasures himself in ways that might have made Onan blush.
This is the Victorian Age. It is the time of Oscar Wilde. Fully unclothed, Mr. Oliver Worthington is engaged in what then is regarded as a perverted act. The same Constable approaches: "You there. Stop!" the Constable yells.
The Constable rushes toward Mr. Worthington and wrestles the naked masturbator to the ground. Mr. Worthington protests, still not comprehending his circumstance. "I was only masturbating to relieve my RLS," Mr. Worthington urges. "RLS," and who might that be"? asks the Constable. Mr. Oliver Worthington is mute. "And what 'ave we got 'ere"? the Constable asks. Reaching into the nearby trousers, the Constable retrieves the still uncleaned razor. The Constable blows his whistle louder and louder, and taps his nightstick with ever more conviction. He has found Jack the Ripper!
Epilogue
Rod Serling again appears.
"Mr. Oliver Worthington was confined for the remainder of his life in a home for the incurably insane, masturbating to relieve his RLS. History, however, does not record the fate of Abigail and Derek St. James. We do not know how, whether or when they ever returned to their former circumstance. But wherever they are, we hope that they are enjoying heterosexual sex ...in The Twilight Zone."
Hello RLSIconoclastMany thanks for your reply. Yes it is difficult to mention names . You are right, it might cause offense for those inadvertently missed.
The irony that the person who first diagnosed this illness hit upon the best treatment so far, has not gone unnoticed by myself. Little more progress in hundreds of years, although I'm grateful to have the opiates at the moment. Whenever I have been admitted to hospital there seems to be a strong reaction to being prescribed opiates . But it is an excellent pain reliever, and works well for my RLS. I have been thinking of a private neurologist for RLS, but fear being offered Methadone. To have to attend a pharmacy and receive an injection, and being viewed almost as a criminal doesn't appeal to me either.
I can empathise with you about the difficulties in getting a diagnosis for the possible pulmonary/cardio illness. It took three years to get a diagnosis for Crohn's disease for myself and in that time I went downhill. Nothing showed on MRI scans and other investigative procedures. I was on a feeding tube for 8 months, and finally admitted for an emergency re-section of the small intestine, where they removed 3 feet of diseased small bowel. Its frustrating when a diagnosis is difficult to achieve , and you know that something is wrong. My faith in technology/doctors took a battering at that time. I hope that you do get a diagnosis soon.
Your description of waiting for the wretched RLS to reach its zenith before letting you go resonates with me. Bonne chance .my friend.
Update:
Though I had been prescribed 1 x 75 mg pregabalin three times daily (not to exceed 225 mg within 24 hours), I found that the first dose @ ~10:00 PM was superfluous, and that each succeeding dose offered only about two hours relief.
As an experiment, within the past 24 hours, I took only 1 x 75 mg pregabalin. I took the single capsule @ ~1:45 AM this morning. Voila! I slept, with torso and limbs fully on my bed, "crotch pillow" separating my legs, from ~2:00 AM - ~9:00 AM.
I think that further experimentation with dose timing may be in order. Perhaps only 1 x 75 mg @ Midnight? Or perhaps 1 x 75 mg every eight hours?
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